Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.
Cell
; 165(2): 434-448, 2016 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-26997484
ABSTRACT
Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D that inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto de Actina
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Ataxias Espinocerebelares
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Proteínas Adaptadoras de Transdução de Sinal
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Proteína 2 Relacionada a Actina
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Proteína 3 Relacionada a Actina
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Canais de Potássio Shaw
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article